Use this site to develop the concepts surrounding cardiovascular drugs and their mechanism of action.
Drugs used for cardiovascular diseases are Statins, ACE inhibitors, Beta blockers, Amiodarone and Digoxin.
These drugs help the heart by dialating the blood vessels to improve blood flow, and block harmful substances in the blood. They also help in improving the hearts ability to relax and to slow the heart rate, and to improve the hearts pumping ability.
Calcium channel blockers block voltage gated calcium channels in cardiac muscle and blood vessels, which prevents the influx of calcium into cells and thus reduce muscle contraction in the heart and in blood vessels. As a result, there is a decrease in cardiac contractility and a decrease in contraction of vascular smooth muscle, which leads to vasodilatation. Ultimately, calcium channel blockers, such as nifedipine and verapamil, cause blood pressure to decrease and thus are prescribed to individuals that have high blood pressure or are hypertensive. Side effects include dizziness, gingival enlargements, constipation, angioedema, etc.
ACE inhibitors work by preventing the conversion of angiotensin I to angiotensin II. Renin from the kidney stimulates production of angiotensin I. ACE inhibitors inhibit ACE (angiotensin converting enzyme), which is the enzyme that converts angiotensin I to II. Angiotensin II normally causes vasoconstriction by promoting sodium retention and inactivates bradykinin, bradykinin is a vasodilator. This leads to a decrease in blood pressure. Side effects include cough, dizziness, headache, fatigue, angioedema. Captopril, ACEI, causes taste disturbances and promotes the excretion of zinc.
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Beta blockers prevent the stimulation of beta receptors. Beta receptors ( beta1 and beta2), when stimulated by epinephrine for example, induce and increase in rate, contractility, automaticity, and conduction velocity of the heart. Therefore, when beta blockers block beta receptors in the heart, there is a decrease in blood pressure. Side effects include bradycardia, hypotension, dizziness, nausea, fatigue diarrhea, etc. Beta blockers such as esmolol, propanolol, and atenolol help reduce hypertension and are indicated for heart failure, myocardial infarction, and so on.
Arrhythmias occur when the electrical stimulation system of the heart is disturb and thus lead to an abnormal heart beat or an increase or decrease in heart rate. Typically, arrhythmias tend to occur when individuals have one or more of the following: diabetes, smoke tobacco, consume alcohol, caffeine, medications, and/or have cardiovascular ailments such as coronary heart disease. The SA node, located in the right atria and known as the pacemaker of the heart, initiates heartbeats by sending an electrical signal to the A-V node. Then the A-V node sends the electrical signal to fibers, located in the His-Purkinje system, that transmit the electrical signal to the ventricles of the heart. Arrhythmias occurs when the SA node is not working properly, causing an abnormal heart rhythm or rate, when the electrical pathway between the SA node and the His-Purkinje system is disrupted, or when a different region of the heart assumes the pacemaker role.
Origins of Arrythimas
Thought to originate from abnormal impulse generation, impulse conduction, or both in combination. Some are caused by increased automaticity, which is usually an increase in the rate of diastolic depolarization (increased slop of phase 4) in pacemaker cells. This phase can also be altered by autonomic nervous system activity or by drugs. Changes in MDP and threshold potential voltage can also affect automaticity. Abnormal impulse generation may also be triggered by drugs, disease, or other disturbances. The induced afterdepolarizations may be early or delayed and can result in sustained tachyarrhythmias.
Reentry is the conduction in branch A is normal, whereas impulses in branch B can proceed in only the reverse direction. A normal conducted impulse through branch A can then be conducted in retrograde fashion through branch B to reexcite an area of tissue (point R) that was previously excited by the normal path of conduction. Reentry is usually the major contributor to atrial fibrillation, an arrhythmia especially common in the elderly.
Heart block is another conduction abnormality. This occurs in response to impaired conduction in the AV node or conducting tissues of the ventricular myocardium. The simplest form is the first-degree block, where there is excessive delay between atrial and ventricular depolarizations, resulting in a prolonged PR interval. In more advanced forms, some (second-degree block) or all (third-degree block) of the impulses from the SA node are prevented from reaching the ventricles, resulting in a ventricular rate that is lower than the atrial rate.
Antiarrhythmic drugs.
Used to treat a wide variety of Atrial and Ventricular arrhythmias ex. Disopyramide phosphate § Action potential – All class I anti-arrhythmics suppress arrhythmias by blocking the sodium channels in the cell membrane during action potential, thereby interfering with the conduction of impulses along adjacent cardiac cells and producing a more membrane stabilizing effect. The cardiac action potential occurs in five phases. Class I anti-arrhythmics exert their effects during different phases of the action potential, binding quickly to sodium channels that are open or inactivated before repolarization occurs in the cell; they are most effective on tachycardia type rhythms. PHASE 4: This coincides with ventricular diastole and marks the resting membrane potential between -85 and -95 mV PHASE 0: During this phase, sodium enters the cell and rapid depolarization takes place. Class IA and IB anti-arrhythmics slow this phase of action potential, class IC anti-arrhythmics markedly slow the phase. PHASE 1: During this phase sodium channels are inactivated PHASE 2: During this plateau phase, sodium levels are equalized. PHASE 3: This marks when potassium leaves the cell and repolarization occurs. Class IA antiarrhythmics work during this phase to block sodium channels. Active transport via the sodium-potassium pump begins restoring the potassium to the inside of the cell and sodium to the outside of the cell. PHASE 4: By this phase, potassium has left the cell, the cell membrane is impermeable to sodium, and the resting potential is restored. Then the cycle begins again.
§ Adverse reactions –Diarrhea, Cramping, Nausea, Vomiting, Anorexia, Bitter taste, Induce arrhythmias § Dental implications – Because some antiarrhythmic agents may depress cardiovascular function, the potential for an increase incidence of orthostatic hypotension and hypotensive syncope exists. Also a greater probability that arrhythimas will develop in a patient when a previous history of arrhythimas who is undergoing stressful treatment. May need med consult. Veramapil, a calcium channel blocker, works by interfering with the slow inward current of pacemaker cells, located in the SA node and thus depresses the rate of phase 4 depolarization. As a result, automaticity in the SA node and the AV node is decreased, which ultimately leads to reduce conduction velocity and increase refractory period of the AV node.
Lidocaine- works by decreasing automaticity of the heart and it particularly effects the ventricles of the heart. Lidocaine blocks sodium channels that are in the inactive stage. Lidocaine tend to shorten ERP and reduces delayed afterdepolarizations from digoxin toxicity.
Propranolol, a beta blocker, works by decreasing automaticity and conduction velocity and thus increases refractory period. This occurs because propranolol is an antagonist of beta receptors of the heart.
Antiarrhythmic treatments:
Class I drugs: Na+ channel blockers
Class II drugs: mainly beta-receptor antagonist
Class III drugs: K+ channel blockers and others
Class IV drugs: Ca+ channel blockers
§ Cardiac glycosides
Describe and their indication for use: Are used for the treatment of congestive heart failure and the management of atrial flutter and fibrillation. Cardiac glycosides are also known as digitalis. These drugs are not considered a first line defense. Pharmocological effects- major effect on the failing heart is to increase the force and strength of contraction of the myocardium (positive inotropic effect) This allows the heart to do more work without increasing its oxygen use. The heart rate is increased for s short amount of time as the Digoxin increases the cardiac output is decreased which will then decrease the heart rate. Mechanism of Action: it has a direct effect on the heart by increasing the force of contraction. · It inhibits sodium potassium activated adenosine triphosphate, an enzyme that regulates the amount of sodium and potassium inside the cell. · Promotes movement of calcium from extracellular to intracellular cytoplasm and strengthens myocardial contraction · Acts on the central nervous system to enhance vagal tone, slowing contractions through the sinoatrial and artioventricular nodes and providing an antiarrhythmic effect. Pharmacodynamics: Digoxin (Drug of choice in US) is used to treat heart failure because it boosts intracellular calcium at the cell membrane, enabling stronger heart contractions. Digoxin may also enhance the movement of Calium into the myocardial cells and stimulate the release, or block the reuptake, of norepinephrine at the adrenergic nerve terminal. Digoxin acts on the CNS to slow the heart rate, thus making it useful for treating supraventricular arrhythmias ( an abnormal heart rhythum that originates above the bundle branches of the hearts conduction system), such as atrial fibrillation and atrial flutter. It also increases the refactory period (the period when the cells of the conduction system can’t conduct an impulse). Indications for use: Heart failure, Atrial Fibrillation and flutter, Supraventricular tachycardia Dental management of patient taking Digoxin:s watch for overdose side effects such as nausea, vision changes, and copious salivation, use epinephrine with caution to minimize arrhythmias, monitor pulse to check for bradycardia, and be aware that tetracycline and erythromycin can increase digoxin levels.
Anti-anginal drugs
· How antianginal drugs work- Angina occurs when the coronary arteries, the hearts primary source of oxygen, supply insuffient oxygen to the myocardium. This increases the hearts workload, increasing heart rate, preload (blood volume in the ventricles at end of diastole), afterload (pressure in the arteries leading from the ventricles), and force of myocardial contractility. The antianginal drugs relieve angina by decreasing one or more of these four factors. · Action potential- 1)Nitrites and Nitrates: are the drug of choice for relieving acute angina. Adverse reactions- headaches, Orthostatic hypotension, reflex tachycardia, cerebral ischemia, weakness, dizziness, flushing, and syncope 2)Beta adrenergic blockers: for long term prevention of angina Adverse reactions- bronchoconstriction, prevent the normal response to insulin-produced hypoglycemia in susceptible patients, heart failure 3)Calcium Channel blockers: Used when other drugs fail to prevent angina Adverse reactions- dizziness, headache, and nausea, hypotension, reflex tachycardia, and peripheral edema Dental implications- Can be precipitated by physical or emotional stress. Because these situations often occur in dental offices, we need to be aware. RMH, make sure nitroglycerin is available (replace after 6 months) and patient’s medication should be placed on the counter. Patient should be treated in a supine on upright position but not standing up because it could lead to syncope.
treatment and prevention during and immediately after myocardial infarction, though this practice is now discouraged given the increased risk of asystole
Use this site to develop the concepts surrounding cardiovascular drugs and their mechanism of action.
Drugs used for cardiovascular diseases are Statins, ACE inhibitors, Beta blockers, Amiodarone and Digoxin.
These drugs help the heart by dialating the blood vessels to improve blood flow, and block harmful substances in the blood. They also help in improving the hearts ability to relax and to slow the heart rate, and to improve the hearts pumping ability.
Calcium channel blockers block voltage gated calcium channels in cardiac muscle and blood vessels, which prevents the influx of calcium into cells and thus reduce muscle contraction in the heart and in blood vessels. As a result, there is a decrease in cardiac contractility and a decrease in contraction of vascular smooth muscle, which leads to vasodilatation. Ultimately, calcium channel blockers, such as nifedipine and verapamil, cause blood pressure to decrease and thus are prescribed to individuals that have high blood pressure or are hypertensive. Side effects include dizziness, gingival enlargements, constipation, angioedema, etc.
ACE inhibitors work by preventing the conversion of angiotensin I to angiotensin II. Renin from the kidney stimulates production of angiotensin I. ACE inhibitors inhibit ACE (angiotensin converting enzyme), which is the enzyme that converts angiotensin I to II. Angiotensin II normally causes vasoconstriction by promoting sodium retention and inactivates bradykinin, bradykinin is a vasodilator. This leads to a decrease in blood pressure. Side effects include cough, dizziness, headache, fatigue, angioedema. Captopril, ACEI, causes taste disturbances and promotes the excretion of zinc.
Beta blockers prevent the stimulation of beta receptors. Beta receptors ( beta1 and beta2), when stimulated by epinephrine for example, induce and increase in rate, contractility, automaticity, and conduction velocity of the heart. Therefore, when beta blockers block beta receptors in the heart, there is a decrease in blood pressure. Side effects include bradycardia, hypotension, dizziness, nausea, fatigue diarrhea, etc. Beta blockers such as esmolol, propanolol, and atenolol help reduce hypertension and are indicated for heart failure, myocardial infarction, and so on.
Arrhythmias occur when the electrical stimulation system of the heart is disturb and thus lead to an abnormal heart beat or an increase or decrease in heart rate. Typically, arrhythmias tend to occur when individuals have one or more of the following: diabetes, smoke tobacco, consume alcohol, caffeine, medications, and/or have cardiovascular ailments such as coronary heart disease. The SA node, located in the right atria and known as the pacemaker of the heart, initiates heartbeats by sending an electrical signal to the A-V node. Then the A-V node sends the electrical signal to fibers, located in the His-Purkinje system, that transmit the electrical signal to the ventricles of the heart. Arrhythmias occurs when the SA node is not working properly, causing an abnormal heart rhythm or rate, when the electrical pathway between the SA node and the His-Purkinje system is disrupted, or when a different region of the heart assumes the pacemaker role.
Origins of Arrythimas
Thought to originate from abnormal impulse generation, impulse conduction, or both in combination. Some are caused by increased automaticity, which is usually an increase in the rate of diastolic depolarization (increased slop of phase 4) in pacemaker cells. This phase can also be altered by autonomic nervous system activity or by drugs. Changes in MDP and threshold potential voltage can also affect automaticity. Abnormal impulse generation may also be triggered by drugs, disease, or other disturbances. The induced afterdepolarizations may be early or delayed and can result in sustained tachyarrhythmias.
Reentry is the conduction in branch A is normal, whereas impulses in branch B can proceed in only the reverse direction. A normal conducted impulse through branch A can then be conducted in retrograde fashion through branch B to reexcite an area of tissue (point R) that was previously excited by the normal path of conduction. Reentry is usually the major contributor to atrial fibrillation, an arrhythmia especially common in the elderly.
Heart block is another conduction abnormality. This occurs in response to impaired conduction in the AV node or conducting tissues of the ventricular myocardium. The simplest form is the first-degree block, where there is excessive delay between atrial and ventricular depolarizations, resulting in a prolonged PR interval. In more advanced forms, some (second-degree block) or all (third-degree block) of the impulses from the SA node are prevented from reaching the ventricles, resulting in a ventricular rate that is lower than the atrial rate.
Antiarrhythmic drugs.
Used to treat a wide variety of Atrial and Ventricular arrhythmias ex. Disopyramide phosphate
§ Action potential – All class I anti-arrhythmics suppress arrhythmias by blocking the sodium channels in the cell membrane during action potential, thereby interfering with the conduction of impulses along adjacent cardiac cells and producing a more membrane stabilizing effect. The cardiac action potential occurs in five phases. Class I anti-arrhythmics exert their effects during different phases of the action potential, binding quickly to sodium channels that are open or inactivated before repolarization occurs in the cell; they are most effective on tachycardia type rhythms.
PHASE 4: This coincides with ventricular diastole and marks the resting membrane potential between -85 and -95 mV
PHASE 0: During this phase, sodium enters the cell and rapid depolarization takes place. Class IA and IB anti-arrhythmics slow this phase of action potential, class IC anti-arrhythmics markedly slow the phase.
PHASE 1: During this phase sodium channels are inactivated
PHASE 2: During this plateau phase, sodium levels are equalized.
PHASE 3: This marks when potassium leaves the cell and repolarization occurs. Class IA antiarrhythmics work during this phase to block sodium channels. Active transport via the sodium-potassium pump begins restoring the potassium to the inside of the cell and sodium to the outside of the cell.
PHASE 4: By this phase, potassium has left the cell, the cell membrane is impermeable to sodium, and the resting potential is restored. Then the cycle begins again.
§ Adverse reactions – Diarrhea, Cramping, Nausea, Vomiting, Anorexia, Bitter taste, Induce arrhythmias
§ Dental implications – Because some antiarrhythmic agents may depress cardiovascular function, the potential for an increase incidence of orthostatic hypotension and hypotensive syncope exists. Also a greater probability that arrhythimas will develop in a patient when a previous history of arrhythimas who is undergoing stressful treatment. May need med consult.
Veramapil, a calcium channel blocker, works by interfering with the slow inward current of pacemaker cells, located in the SA node and thus depresses the rate of phase 4 depolarization. As a result, automaticity in the SA node and the AV node is decreased, which ultimately leads to reduce conduction velocity and increase refractory period of the AV node.
Lidocaine- works by decreasing automaticity of the heart and it particularly effects the ventricles of the heart. Lidocaine blocks sodium channels that are in the inactive stage. Lidocaine tend to shorten ERP and reduces delayed afterdepolarizations from digoxin toxicity.
Propranolol, a beta blocker, works by decreasing automaticity and conduction velocity and thus increases refractory period. This occurs because propranolol is an antagonist of beta receptors of the heart.
Antiarrhythmic treatments:
Class I drugs: Na+ channel blockers
Class II drugs: mainly beta-receptor antagonist
Class III drugs: K+ channel blockers and others
Class IV drugs: Ca+ channel blockers
§ Cardiac glycosides
Describe and their indication for use: Are used for the treatment of congestive heart failure and the management of atrial flutter and fibrillation. Cardiac glycosides are also known as digitalis. These drugs are not considered a first line defense.
Pharmocological effects- major effect on the failing heart is to increase the force and strength of contraction of the myocardium (positive inotropic effect) This allows the heart to do more work without increasing its oxygen use. The heart rate is increased for s short amount of time as the Digoxin increases the cardiac output is decreased which will then decrease the heart rate.
Mechanism of Action: it has a direct effect on the heart by increasing the force of contraction.
· It inhibits sodium potassium activated adenosine triphosphate, an enzyme that regulates the amount of sodium and potassium inside the cell.
· Promotes movement of calcium from extracellular to intracellular cytoplasm and strengthens myocardial contraction
· Acts on the central nervous system to enhance vagal tone, slowing contractions through the sinoatrial and artioventricular nodes and providing an antiarrhythmic effect.
Pharmacodynamics: Digoxin (Drug of choice in US) is used to treat heart failure because it boosts intracellular calcium at the cell membrane, enabling stronger heart contractions. Digoxin may also enhance the movement of Calium into the myocardial cells and stimulate the release, or block the reuptake, of norepinephrine at the adrenergic nerve terminal. Digoxin acts on the CNS to slow the heart rate, thus making it useful for treating supraventricular arrhythmias ( an abnormal heart rhythum that originates above the bundle branches of the hearts conduction system), such as atrial fibrillation and atrial flutter. It also increases the refactory period (the period when the cells of the conduction system can’t conduct an impulse).
Indications for use: Heart failure, Atrial Fibrillation and flutter, Supraventricular tachycardia
Dental management of patient taking Digoxin:s watch for overdose side effects such as nausea, vision changes, and copious salivation, use epinephrine with caution to minimize arrhythmias, monitor pulse to check for bradycardia, and be aware that tetracycline and erythromycin can increase digoxin levels.
Anti-anginal drugs
· How antianginal drugs work- Angina occurs when the coronary arteries, the hearts primary source of oxygen, supply insuffient oxygen to the myocardium. This increases the hearts workload, increasing heart rate, preload (blood volume in the ventricles at end of diastole), afterload (pressure in the arteries leading from the ventricles), and force of myocardial contractility. The antianginal drugs relieve angina by decreasing one or more of these four factors.
· Action potential-
1) Nitrites and Nitrates: are the drug of choice for relieving acute angina.
Adverse reactions- headaches, Orthostatic hypotension, reflex tachycardia, cerebral ischemia, weakness, dizziness, flushing, and syncope
2) Beta adrenergic blockers: for long term prevention of angina
Adverse reactions- bronchoconstriction, prevent the normal response to insulin-produced hypoglycemia in susceptible patients, heart failure
3) Calcium Channel blockers: Used when other drugs fail to prevent angina
Adverse reactions- dizziness, headache, and nausea, hypotension, reflex tachycardia, and peripheral edema
Dental implications- Can be precipitated by physical or emotional stress. Because these situations often occur in dental offices, we need to be aware. RMH, make sure nitroglycerin is available (replace after 6 months) and patient’s medication should be placed on the counter. Patient should be treated in a supine on upright position but not standing up because it could lead to syncope.
Heart failure:
Propranolol also shows some class I action
Sotalol is also a beta blocker[[#cite_note-pmid11350865-6|[7]]]